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P158. Relationship between thiopurine metabolite levels and endoscopic improvement in patients with postoperative moderate to severe endoscopic recurrence of Crohn's disease

S. Angelberger1, E. Schaeffeler2, A. Teml2, W. Petritsch3, O. Shonova4, M. Lukáš5, S. Bar-Meir6, R. Greinwald7, R. Mueller7, E.F. Stange8, K.R. Herrlinger8, M. Schwab2, W. Reinisch1

1Medical University of Vienna, Vienna, Austria; 2Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany; 3Medical University of Graz, Graz, Austria; 4Nemocnice Ceske Budejovice, Ceske Budejovice, Czech Republic; 5Klinické centrum Iscare Lighthouse, Prague, Czech Republic; 6Chaim Sheba Medical Centre Tel Hashomer, Tel Hashomer, Israel; 7Dr. Falk Pharma GmbH, Freiburg, Germany; 8Robert-Bosch Krankenhaus, Stuttgart, Germany

Introduction: Endoscopic recurrence of Crohn's disease (CD) after curative ileocecal resection precedes clinical relapse. Azathioprine (AZA) reduces the risk of both clinical and endoscopic recurrence.

Aim: To evaluate the association between thiopurine metabolite levels and endoscopic improvement in CD patients with moderate to severe postoperative endoscopic recurrence (PER).

Methods: Patients treated with AZA within the previously published AZT-2 study were included. Ileocolonoscopy was performed at baseline and at week 52 or at premature discontinuation (median 364 days). Red blood cell concentrations (RBC) of 6-thioguanine nucleotides (6-TGN), 6-methyl-mercaptopurine ribonucleotides (6-MMPR), and 6-methyl-thioguanine nucleotides (6-MTGN) were measured by HPLC assay. A cut-off value of 6-TGN of ≥235 pmol/8×108 RBC was used as established in literature. Endoscopic improvement was defined as a reduction of the endoscopic score by Rutgeerts et al. by at least one point, and mucosal healing.

Results: Endoscopic data were available on 31 patients treated with azathioprine (f/m = 13/18, median age: 32 years, median AZA dose: 2.24 mg/kg/d) for median 358 days. At last observation, the median levels of 6-TGN (n = 26), 6-MMPR (n = 27), and 6-MTGN (n = 26) were 139.7, 1696.1 and 70.1 pmol/8×108 RBC, respectively. Endoscopic score improved from i3-i4 to i0-i2 (p = 0.004). Mucosal healing was achieved in 6/31 (19.4%) of patients. High 6-TGN levels (n = 8) were associated with a significantly higher drop in the Rutgeerts score than low 6-TGN (n = 18) levels (median drop of 3 vs 1, p = 0.023). There was no difference concerning mucosal healing (p = 0.33). Furthermore, there was no correlation between 6-MMPR and 6-MTGN levels and endoscopic improvement.

Conclusion: Our data suggest that high 6-TGN levels may be linked to endoscopic improvement in patients with PER of CD.

Supported by Dr. Falk Pharma GmbH, Freiburg, Germany.